Induction of Autoantibody-Mediated Spontaneous Arthritis Critically Depends on Follicular Dendritic Cells
2009; Cell Press; Volume: 30; Issue: 1 Linguagem: Inglês
10.1016/j.immuni.2008.10.019
ISSN1097-4180
AutoresPanayiotis Victoratos, George Kollias,
Tópico(s)Monoclonal and Polyclonal Antibodies Research
ResumoFollicular dendritic cells (FDCs) are important for the induction of protective T cell-dependent humoral responses, but their contribution to autoimmunity remains elusive. Here, gene-targeted interruption of FDC development was combined with the K/BxN mouse model of arthritis. We found that FDCs were essential for autoantibody production through two distinct but cooperative functions. In a T cell-independent fashion, FDCs loaded with autoantigen-containing immune complexes supported germinal center (GC) B cell development. Additionally, the integrity of FDC networks was required for the recruitment of arthritogenic follicular helper T cells, a process that drove T-B cell interactions and productive GC reactivity. Importantly, pharmacological interference in the maintenance of FDCs ameliorated disease development, suggesting the FDC as a potential target for dampening autoimmunity.
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